Specific Objective: To obtain partial funding for the 3rd International MDM2 Meeting to enable young US trainees (graduate students and post docs) and US speakers to attend the meeting. Scientific Description: The MDM2 protein is the principal negative regulator of the tumor suppressor protein p53. MDM2, a p53-specific E3 ubiquitin lipase, mediates p53 degradation via the 26S proteasome pathway, thus keeping p53 levels in unstressed cells very low. Stress-induced posttranslational modifications of p53 disrupt the p53-MDM2 complex, thereby rapidly stabilizing p53 levels during a stress response. Accordingly, small molecule inhibitors of the p53-MDM2 complex hold great promise for development of novel cancer therapies in tumors that retain wild type p53 (about 50%) and are being vigorously developed by academic laboratories as well as by some major pharmaceutical companies. Conversely, amplification of MDM2 expression and its homolog MDMX by various means is an oncogenic pathway that suppresses the p53 tumor suppressive action and is realized in many human tumors. Participants: About 25-30 scientists from the USA, Canada, Europe, UK, Israel and Asia will give talks to present their latest findings. Based on previous attendances, we anticipate that 150-180 international scientists will attend the Meeting. Goals: Two International MDM2 Meetings dedicated to this rapidly growing field have been held to date. The agenda for the 3rd MDM2 Meeting is to discuss the newest MDM2 research in the context of the broader fields of tumor genesis, p53 tumor suppression, cell cycle control and apoptosis, and early mammalian development. Another focus will be MDM2 as a rational drug target. In this regard, a few invited speakers will be from the pharmaceutical industry working on such drugs. Topics convered: Structure and Function of MDM2, Stress Signaling Upstream of MDM2: Regulation of MDM2 by Posttranslational Modifications, Regulation of MDM2 function by Protein-Protein interactions, MDM2 Family members, Animal Models and Clinical Associations, Mdm2 proteins as therapeutic targets, other p53 Ubiquitin lipases and p53 Deubiquitylase.